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The growing urgence of information protection promotes continuously the development of information-encryption technique. To date, hydrogels have become an emerging candidate for advanced information-encryption materials, because of their unique stimulus responsiveness. However, current methods to design multi-level information-encrypted hydrogels usually need sophisticated chemistry or experimental setup. Herein, a novel strategy is reported to fabricate hydrogels with multi-level information encryption/decryption functions through spatially programming the polymorphic crystal phases. As homocrystalline and stereocomplex crystal phases in fluorescent hydrogels have different solvent stabilities, the transparency and fluorescence of the hydrogels can be regulated, thereby enabling the multi-level encryption/decryption processes. Moreover, the structural origins behind these processes are discussed. It is believe that this work will inspire future research on developing advanced information-encryption materials upon programming the polymer crystal structure.
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PURPOSE: The aim of the study was to investigate the effect of liquiritin on neuroendocrine-immune network in menopausal rat model. METHODS: Liquiritin groups were respectively given liquiritin suspension at the dose of 80, 40, and 20 mg/kg, once a day for continuous 30 days after the removal of bilateral ovaries to induce the menopausal rat model. Behavioral experiments were conducted and the organs were weighed for the viscera index. The content of estradiol (E2 ) and follicle-stimulating hormone (FSH) in the serum and 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in hypothalamus were assayed by enzyme linked immunosorbent assay kits. Morphological changes of uterus and adrenal gland were observed by hematoxylin-eosin (HE) staining and estrogen receptor (ER) expression of uterus and spleen were determined by immunohistochemical staining. RESULTS: For the nervous system, liquiritin relieved menopausal depression and up-regulated the levels of 5-HT and NE in hypothalamus; for the endocrine system, it raised the concentrations of E2 and FSH in serum, relieved the histological changes of uterus and adrenal gland and increased the expression of ER in uterus; for the immune system, it increased the thymus index and the expression of ER in spleen. CONCLUSIONS: Liquiritin improved menopausal syndrome in multiple ways by affecting the neuro-endocrine-immune network.
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Flavanonas/uso terapêutico , Glucosídeos/uso terapêutico , Glycyrrhiza/química , Menopausa/efeitos dos fármacos , Sistemas Neurossecretores/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Feminino , Flavanonas/farmacologia , Glucosídeos/farmacologia , Ratos , Ratos WistarRESUMO
The objective of this experiment was to test the effect of supplementation of analogues of methionine 2-hydroxy-4-methylthio butanoic acid isopropyl ester (HMBi) on growth, digestibility, antioxidant index, abundance and composition of rumen bacterial community in Xiangdong Black Goats. Thirty-six growing Xiangdong Black Goats were divided into four groups in such a way that each group had three replicate and each replicate had three animals. Experimental groups were assigned four levels of HMBi in basal diet: 0% HMBi (on dietary DM basis); 0.05% HMBi; 0.10% HMBi and 0.20% HMBi. Goats fed 0.10% HMBi in basal diet had higher average daily weight gain (p < .05). Goats fed 0.05% HMBi had higher apparent digestibility of gross energy (p < .01). The group 0% HMBi supplementation had a higher level of superoxide dismutase and malondialdehyde (p < .01). The goats fed 0.20% HMBi in basal diet had a higher level of insulin and leptin (p < .01) than 0% HMBi supplementation goats. 16S rRNA high-throughput sequencing analysis revealed similarities in the community composition, species diversity and relative abundance of dominant bacteria at the phylum and genus levels among the four groups. In conclusion, HMBi supplementation has no negative effect on apparent digestibility, antioxidant index and the ruminal bacteria composition. Therefore, 0.10% supplementation of HMBi is recommended in the diet of goats to improve the growth performance.
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Ração Animal , Butiratos/farmacologia , Digestão/efeitos dos fármacos , Cabras/fisiologia , Rúmen/microbiologia , Animais , Antioxidantes/metabolismo , Bactérias/classificação , Bactérias/efeitos dos fármacos , Butiratos/administração & dosagem , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Feminino , Cabras/sangueRESUMO
Daphne genkwa Sieb.et Zucc. is a well-known medicinal plant. This study was designed to apply the ultra-high performance liquid chromatography system to establish a quality control method for D. genkwa. Data revealed that there were 15 common peaks in 10 batches of D. genkwa Sieb. Et Zucc. (Thymelaeaceae) from different provinces of China. On this basis, the fingerprint chromatogram was established to provide references for quality control. Afterwards, the chemical constitutions of these common peaks were analyzed using the UPLC-Q-TOF-MS system and nine of them were identified. In addition, LPS-stimulated RAW264.7 murine macrophages and DPPH assay were used to study the anti-inflammatory and anti-oxidation effects of D. genkwa. Then the fingerprint-efficacy relationships between UPLC fingerprints and pharmacodynamic data were studied with canonical correlation analysis. Analysis results indicated that the anti-inflammatory and anti-oxidation effects differed among the 10 D. genkwa samples owing to their inherent differences of chemical compositions. Taken together, this research established a fingerprint-efficacy relationship model of D. genkwa plant by combining the UPLC analytic technique and pharmacological research, which provided references for the detection of the principal components of traditional Chinese medicine on bioactivity.
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Anti-Inflamatórios/química , Antioxidantes/química , Cromatografia Líquida de Alta Pressão/métodos , Daphne/química , Espectrometria de Massas/métodos , Extratos Vegetais/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/análise , Compostos de Bifenilo/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Picratos/análise , Picratos/metabolismo , Extratos Vegetais/farmacologia , Células RAW 264.7 , Reprodutibilidade dos TestesRESUMO
Staphylococcus aureus is one of the main pathogens involved in dairy cow mastitis. Monitoring of antibiotic use would prove useful to assess the risk of Staph. aureus in raw milk. The objective of this work was to investigate the prevalence of Staph. aureus strais isolated from raw milk in northern China, and to characterize antimicrobial susceptibility of these strains and their key virulence genes. In total, 195 raw milk samples were collected from 195 dairy farms located in 4 cities of northern China from May to September 2015. Out of 195 samples, 54 (27.7%) were positive for Staph. aureus. Among these 54 samples, 54 strains of Staph. aureus were isolated, and 16 strains were identified as methicillin-resistant Staph. aureus. The strains exhibited high percentages of resistance to penicillin G (85.2%), ampicillin (79.6%), and erythromycin (46.3%). Moreover, 72% of the strains showed resistance to more than one antimicrobial agent. Overall, 63% of penicillin-resistant strains possessed the blaZ gene, and 60% of the erythromycin-resistant strains possessed erm(A), erm(B), erm(C), msr(A), or msr(B) genes with 8 different gene patterns. All isolates resistant to gentamicin, kanamycin, and oxacillin carried the aac6'-aph2", ant(4')-Ia, and mecA genes, respectively. Two tet(M)-positive isolates carried specific genes of the Tn916-Tn1545 transposon. The most predominant virulence genes were sec, sea, and pvl, which encode staphylococcal enterotoxins (sec and sea) and Panton-Valentine leukocidin, respectively. Thirty-two isolates (59.2%) harbored one or more virulence genes. The majority of Staph. aureus strains were multidrug resistant and carried multiple virulence genes, which may pose a risk to public health. Our data indicated that antimicrobial resistance of Staph. aureus was prevalent in dairy herds in northern China, and that antibiotics, especially penicillin G and ampicillin, to treat mastitis caused by Staph. aureus should be used with caution in northern China.
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Mastite Bovina/microbiologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/isolamento & purificação , Animais , Antibacterianos , Toxinas Bacterianas , Bovinos , China/epidemiologia , Farmacorresistência Bacteriana , Enterotoxinas/genética , Exotoxinas , Feminino , Leucocidinas , Mastite Bovina/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Virulência/efeitos dos fármacosRESUMO
The quality of pasteurized milk is commonly assessed through microbiological analysis, with variations in storage conditions significantly impacting the suppression of bacterial growth throughout the milk's shelf life. This study investigated the dynamics of total bacterial counts (TBCs) and bacterial community shifts in milk that underwent pasteurization at 80 °C for 15 s. The milk was subsequently stored at 4 °C for varying intervals of 1, 4, 7, 10, 13, and 16 days. Culture-based testing revealed a significant TBC increase during the storage period spanning 1 to 16 days (up to -log10 4.2 CFU/mL at day 16). The TBC in pasteurized milk exhibited accelerated microbial growth from day 13 onwards, ultimately peaking on day 16. Bacillus was detected through 16S rRNA identification. Principal component analysis demonstrated a significant impact of storage time on bacterial communities in pasteurized milk. Analysis of bacterial diversity revealed a negative correlation between the Shannon index and the duration of pasteurized milk storage. Using high-throughput sequencing, Streptococcus and Acinetobacter were detected as prevalent bacterial genera, with Streptococcus dysgalactiae and Streptococcus uberis showing as dominant taxa. The presence of Streptococcus dysgalactiae and Streptococcus uberis in pasteurized milk might be attributed to the initial contamination from raw milk with mastitis. This study offers new evidence of the prevalence of bacterial community in pasteurized milk, thereby adding value to the enhancement of quality control and the development of strategies for reducing microbial risks.
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The motility pattern of the reticulo-rumen is a key factor affecting feed intake, rumen digesta residence time, and rumen fermentation. However, it is difficult to study reticulo-ruminal motility using general methods owing to the complexity of the reticulo-ruminal structure. Thus, we aimed to develop a technique to demonstrate the reticulo-ruminal motility pattern in static goats. Six Xiangdong black goats (half bucks and half does, body weight 29.5 ± 1.0 kg) were used as model specimens. Reticulo-ruminal motility videos were obtained using medical barium meal imaging technology. Videos were then analyzed using image annotation and the centroid method. The results showed that reticulo-ruminal motility was divided into primary (stages I, II, III, and IV) and secondary contraction, and the movements of ruminal digesta depended on reticulo-ruminal motility. Our results indicated common motility between the ruminal dorsal sac and ruminal dorsal blind sac. We observed that stages I (3.92 vs. 3.21 s) (P < 0.01), II (4.81 vs. 4.23 s) (P < 0.01), and III (5.65 vs. 5.15 s) (P < 0.05); interval (53.79 vs. 50.95 s); secondary contraction time (10.5 vs. 10 s); and were longer, whereas stage IV appeared to be shorter in the bucks than in the does (7.83 vs. 14.67 s) (P < 0.01). The feasibility of using barium meal imaging technology for assessing reticulo-ruminal and digesta motility was verified in our study. We determined the duration of each stage of reticulo-ruminal motility and collected data on the duration and interval of each stage of ruminal motility in goats. This research provides new insights for the study of gastrointestinal motility and lays a solid foundation for the study of artificial rumen.
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The beef cattle industry in China has advanced remarkably since its reform and opening up; consequently, China has become the world's third-largest beef cattle producer. China is also one of the countries with the most substantial research input and output in the field of beef cattle feed and nutrition. The progress and innovation by China in the research field of beef cattle feed and nutrition have undoubtedly promoted the development of the domestic beef cattle industry. This review summarizes recent advances in feed resource development, nutrient requirements, and nutritional regulation of beef cattle in China. Limitations in current research and perspectives on future work are also discussed.
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Introduction: Rumen motility is a key element that influences ruminant nutrition, whereas little is known about the effects of rumen contraction duration on rumen fermentation and ruminal microbiome. We previously reported that proper rotation speed of a rumen simulation technique (RUSITEC) system enhanced rumen fermentation and microbial protein (MCP) production. In the present study, different contraction durations and intervals were simulated by setting different stirring times and intervals of the stirrers in a RUSITEC system. The objective of this trial was to evaluate the influences of stirring time on rumen fermentation characteristics, nutrient degradation, and ruminal bacterial microbiota in vitro. Methods: This experiment was performed in a 3 × 3 Latin square design, with each experimental period comprising 4 d for adjustment and 3 d for sample collection. Three stirring time treatments were set: the constant stir (CS), the intermittent stir 1 (each stir for 5 min with an interval of 2 min, IS1), and the intermittent stir 2 (each stir for 4 min with an interval of 3 min, IS2). Results: The total volatile fatty acid (TVFA) concentration, valerate molar proportion, ammonia nitrogen level, MCP density, protozoa count, disappearance rates of dry matter, organic matter, crude protein, neutral detergent fiber, and acid detergent fiber, emissions of total gas and methane, and the richness index Chao 1 for the bacterial community were higher (p < 0.05) in the IS1 when compared to those in the CS. The greatest TVFA, MCP, protozoa count, nutrient disappearance rates, gas productions, and bacterial richness indices of Ace and Chao 1 amongst all treatments were observed in the IS2. The relative abundance of the genus Treponema was enriched (p < 0.05) in CS, while the enrichment (p < 0.05) of Agathobacter ruminis and another two less known bacterial genera were identified in IS2. Discussion: It could be concluded that the proper reduction in the stirring time might help to enhance the feed fermentation, MCP synthesis, gas production, and the relative abundances of specific bacterial taxa.
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The purpose of this study is to reveal the effects of different particle sizes of rice straw on the rumen protozoa count, nutrient disappearance rate, rumen fermentation, and microbial community in a rumen simulation technique (RUSITEC) system. In this experiment, a single-factor random trial design was adopted. According to the different particle sizes of rice straw, there were three treatments with three replies in each treatment. Three kinds of goat total mixed ration (TMR), with the same nutrients were used to carry out a 10 days in vitro fermentation experiment using the rumen simulation system developed by Hunan Agricultural University, including 6 days the pretrial period and 4 days formal period. This study found that the organic matter disappearance rate, concentrations of total volatile fatty acids (VFAs), acetate, propionate, and iso-butyrate were greatest in the 4 mm group (p < 0.05). There were no significant differences in the alpha diversity, among the three groups (p > 0.05). The relative abundance of Treponema and Ruminococcus of the 2 mm group increased; the relative abundance of Butyrivibrio and Prevotella in samples increased in the 4 mm group. In addition, the results of correlation analysis showed that Prevotella and Ruminococcus was positively correlated with butyrate, ammonia-N, dOM and d ADF (p < 0.05) and negatively correlated with valerate (p < 0.05); Oscillospira was positively correlated with valerate (p < 0.01) and negatively correlated with propionate, butyrate, ammonia-N, dOM and dADF (p < 0.05). The present results imply that compared to the other groups, rice straw particle size of 4 mm may improve the disappearance rate of nutrients and promote the production of volatile fatty acids by regulating ruminal microorganisms.
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This study was conducted to compare the effects of rumen-protected (RP-Leu) and unprotected L-leucine (RU-Leu) on the fermentation parameters, bacterial composition, and amino acid metabolism in vitro rumen batch incubation. The 5.00 g RP-Leu or RU-Leu products were incubated in situ in the rumen of four beef cattle (Bos taurus) and removed after 0, 2, 4, 6, 12, 16, and 24 h to determine the rumen protection rate. In in vitro incubation, both RP-Leu and RU-Leu were supplemented 1.5 mmol/bottle (L-leucine HCl), and incubated after 0, 2, 4, 6, 8, 12, and 16 h to measure gas production (GP), nutrient degradability, fermentation parameters, bacterial composition, and amino acids metabolism. Results from both in vitro and in situ experiments confirmed that the rumen protection rate was greater (p < 0.01) in RP-Leu than in RU-Leu, whereas the latter was slow (p < 0.05) degraded within incubation 8 h. Free leucine from RP-Leu and RU-Leu reached a peak at incubation 6 h (p < 0.01). RU-Leu supplementation increased (p < 0.05) gas production, microbial crude protein, branched-chain AAs, propionate and branched-chain VFAs concentrations, and Shannon and Sobs index in comparison to the control and RP-Leu supplementation. RU-Leu and RP-Leu supplementation decreased (p < 0.05) the relative abundance of Bacteroidota, which Firmicutes increased (p < 0.05). Correlation analysis indicated that there are 5 bacteria at the genus level that may be positively correlated with MCP and propionate (p < 0.05). Based on the result, we found that RP-Leu was more stable than RU-Leu in rumen fluid, but RU-Leu also does not exhibit rapid degradation by ruminal microbes for a short time. The RU-Leu was more beneficial in terms of regulating rumen fermentation pattern, microbial crude protein synthesis, and branched-chain VFAs production than RP-Leu in vitro rumen conditions.
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Resveratrol (Res) is a bioactive dietary component and alleviates apoptosis in multiple cell types. However, its effect and mechanism on lipopolysaccharide (LPS)-induced bovine mammary epithelial cells (BMEC) apoptosis, which commonly happens in dairy cows with mastitis, is unknown. We hypothesized that Res would inhibit LPS-induced apoptosis in BMEC through SIRT3, a NAD + -dependent deacetylase activated by Res. To test the dose-response effect on apoptosis, 0-50 µM Res were incubated with BMEC for 12 h, followed by 250 µg/mL LPS treatment for 12 h. To investigate the role of SIRT3 in Res-mediated alleviation of apoptosis, BMEC were pretreated with 50 µM Res for 12 h, then incubated with si-SIRT3 for 12 h and were finally treated with 250 µg/mL LPS for 12 h. Res dose-dependently promoted the cell viability and protein levels of Bcl-2 (Linear P < 0.001) but decreased protein levels of Bax, Caspase-3 and Bax/Bcl-2 (Linear P < 0.001). TUNEL assays indicated that cellular fluorescence intensity declined with the rising doses of Res. Res also dose-dependently upregulated SIRT3 expression, but LPS had the opposite effect. SIRT3 silencing abolished these results with Res incubation. Mechanically, Res enhanced the nuclear translocation of PGC1α, the transcriptional cofactor for SIRT3. Further molecular docking analysis revealed that Res could directly bind to PGC1α by forming a hydrogen bond with Tyr-722. Overall, our data suggested that Res relieved LPS-induced BMEC apoptosis through the PGC1α-SIRT3 axis, providing a basis for further in vivo investigations of applying Res to relieve mastitis in dairy cows.
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Doenças dos Bovinos , Mastite , Sirtuína 3 , Feminino , Bovinos , Animais , Resveratrol/farmacologia , Resveratrol/metabolismo , Lipopolissacarídeos/toxicidade , Sirtuína 3/genética , Sirtuína 3/metabolismo , Sirtuína 3/farmacologia , Simulação de Acoplamento Molecular , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Proteína X Associada a bcl-2/metabolismo , Glândulas Mamárias Animais/metabolismo , Células Epiteliais/metabolismo , Mastite/metabolismo , ApoptoseRESUMO
This study comprehensively investigated arsenic's enrichment, distribution, and characteristics in tailings. XRD and SEM-EDS characterized the phase and morphology of tailings from various smelting processes. At the same time, the embedding characteristics of arsenic in the ore phase were analyzed by EPMA. The differences between arsenic's leading ore phase carriers in different recovery processes were found. It was discussed that this phenomenon would be related to the element-binding ability and the precipitation priority of the ore phase. The occurrence state of arsenic was discussed by sequential chemical extraction experiments. The proportion of leachable arsenic is higher than the low-risk limit, whatever which smelting method is adopted, which leads to high environmental risk. In the experiment of comparing the leaching toxicity of tailings by different leaching methods, the arsenic concentration in the leaching solution of tailings recovered by the flotation method exceeds the specified safety range. Although the tailings after reduction smelting did not show high leaching toxicity, a large number of accumulations also would not represent absolute safety.
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Arsênio , Arsênio/química , Cobre , MetaisRESUMO
The present study was performed to evaluate the impacts of tannic acid (TA) supplementation at different levels on the growth performance, physiological, oxidative and immunological metrics, and ruminal microflora of Xiangdong black goats. Twenty-four goats were randomly assigned to four dietary treatments: the control (CON, basal diet), the low-dose TA group [TAL, 0.3 % of dry matter (DM)], the mid-dose TA group (TAM, 0.6 % of DM), and the high-dose TA group (TAH, 0.9 % of DM). Results showed that the growth performance was unaffected (P > 0.05) by adding TA, whilst the 0.3 % and 0.6 % TA supplementation significantly decreased (P < 0.05) the apparent digestibility of crude protein (CP) and ruminal NH3-N concentration, and raised (P < 0.05) the level of total volatile fatty acid (TVFA) in rumen. The increments of alanine aminotransferase (ALT), triglyceride (TG), cortisol (CORT), total antioxidant capacity (T-AOC), interleukin (IL)-1ß, IL-6, and serumamyloid A (SAA), and decrements of globulin (GLB), immunoglobulin G (IgG), cholinesterase (CHE), glutathione reductase (GR), creatinine (CRE), growth hormone (GH), high-density lipoprotein cholesterol (HDLC), and insulin-like growth factor 1 (IGF-1) to different extents by TA addition were observed. Although the Alpha and Beta diversity of rumen bacterial community remained unchanged by supplementing TA, the relative abundance of the predominant genus Prevotella_1 was significantly enriched (P < 0.05) in TAL. It could hence be concluded that the TA supplementation in the present trial generally decreased CP digestion and caused oxidative stress and inflammatory response without influencing growth performance and ruminal microbiota diversity. More research is needed to explore the premium dosage and mechanisms of effects for TA addition in the diet of goats.
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This study was conducted to evaluate the influences of supplementing tannic acid (TA) at different doses on the production performance, physiological and immunological characteristics, and rumen bacterial microbiome of cattle. Forty-eight Holstein bulls were randomly allocated to four dietary treatments: the control (CON, basal diet), the low-dose TA treatment [TAL, 0.3% dry matter (DM)], the mid-dose TA treatment (TAM, 0.9% DM), and the high-dose TA treatment (TAH, 2.7% DM). This trial consisted of 7 days for adaptation and 90 days for data and sample collection, and samples of blood and rumen fluid were collected on 37, 67, and 97 d, respectively. The average daily gain was unaffected (P > 0.05), whilst the ruminal NH3-N was significantly decreased (P < 0.01) by TA supplementation. The 0.3% TA addition lowered (P < 0.05) the levels of ruminal isobutyrate, valerate, and tumor necrosis factor alpha (TNF-α), and tended to (P < 0.1) increase the gain to feed ratio. The digestibility of DM, organic matter (OM), and crude protein, and percentages of butyrate, isobutyrate, and valerate were lower (P < 0.05), while the acetate proportion and acetate to propionate ratio in both TAM and TAH were higher (P < 0.05) than the CON. Besides, the 0.9% TA inclusion lessened (P < 0.05) the concentrations of glucagon and TNF-α, but enhanced (P < 0.05) the interferon gamma (IFN-γ) level and Simpson index of ruminal bacteria. The 2.7% TA supplementation reduced (P < 0.05) the intake of DM and OM, and levels of malondialdehyde and thyroxine, while elevated (P < 0.05) the Shannon index of the rumen bacterial populations. Moreover, the relative abundances of the phyla Fibrobacteres and Lentisphaerae, the genera Fibrobacter and Bradyrhizobium, and the species Bradyrhizobium sp., Lachnospiraceae bacterium RM29, and Lachnospiraceae bacterium CG57 were highly significantly (q < 0.01) or significantly (q < 0.05) raised by adding 2.7% TA. Results suggested that the TA addition at 0.3% is more suitable for the cattle, based on the general comparison on the impacts of supplementing TA at different doses on all the measured parameters.
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SheXiang XinTongNing (XTN), which is composed of six traditional Chinese herbs, is a commercially available Chinese patent medicine that has been widely used as the treatment of coronary heart disease (CHD). Its mechanisms against coronary heart disease, however, remain largely unknown. This study aimed to investigate the pharmacological mechanisms of XTN against CHD via network pharmacology and experimental evaluation. In this study, GO enrichment and KEGG pathway enrichment were firstly performed for acquiring the potentially active constituents of XTN, the candidate targets related to coronary heart disease, the drug-components-targets network as well as the protein-protein interaction network and further predicting the mechanisms of XTN against coronary heart disease. Subsequently, a series of in vitro experiments, specifically MTT assay, flow cytometry and Real-time quantitative polymerase chain reaction analysis, and a succession of in vivo experiments, including Tunel staining and immunohistochemical staining were conducted for further verification. Results showed that Bcl-2, IGF1, CASP3 were the key candidate targets which significantly associated with multiple pathways, namely PI3K-Akt signaling pathway and MAPK signaling pathway. It indicated that the potential mechanism of XTN against CHD may be predominantly associated with cell apoptosis. The in vitro experimental results showed that XTN treatment remarkably decreased the apoptotic rate and Bax/Bcl-2 ratio of H9c2 cells. Histological results confirmed that XTN not only effectively alleviated oxidative damage caused by myocardial ischemia but inhibited cell apoptosis. Given the above, through the combined utilization of virtual screening and experimental verification, the findings suggest that XTN makes a significant contribution in protecting the heart from oxidative stress via regulating apoptosis pathways, which lays the foundations and offers an innovative idea for future research.
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The Chinese patent medicine She-Xiang-Xin-Tong-Ning (SXXTN) is a clinical medication for coronary heart disease (CHD) and angina pectoris. This study aimed to investigate pharmacological effects of SXXTN and elucidate the role in angiogenesis on human umbilical vein endothelial cells (HUVECs) and acute myocardial ischemia (AMI) rats. We prepared SXXTN to treat the cells to reveal their effects on oxidative stress-damaged cell viability, as well as cell proliferation, migration, and tube formation processes. SXXTN was also used to treat coronary artery ligation-induced acute myocardial ischemia rats to confirm whether it had positive effect on myocardial issues by hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC) staining and immunohistochemical staining. We measured the levels of peroxidative damage-related enzymes in cytoplasm and serum by biochemical kits and detected vascular endothelial growth factor (VEGF), angiotensin II (Ang II), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α) levels in cells and rats by enzyme-linked immunosorbent assay (ELISA) kits. The results showed that SXXTN protects HUVECs against oxidative stress damage and reversed the decrease of superoxide dismutase (SOD), glutathione (GSH) and increase of creatine kinase (CK), lactate dehydrogenase (LDH) caused by oxidative stress. SXXTN promoted angiogenesis through stimulating cell migration, tube formation, and activating VEGF/VEGFR2 and ERK1/2 pathways. Furthermore, SXXTN reduced infarct size and inhibited PGI2/TXA2 imbalance, preventing atherosclerosis plaque rupture leading to worsening coronary heart disease. Taken together, we report the first in vivo and in vitro evidence that SXXTN reduced oxidative stress-mediated damage and enhanced angiogenesis, which might be useful in treatment of myocardial infarction.
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Indutores da Angiogênese/uso terapêutico , Corydalis/química , Medicina Tradicional Chinesa , Isquemia Miocárdica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Animais , Cervos , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Rheumatoid arthritis (RA) is one of the most prevalent chronic inflammatory and angiogenic diseases. The aim of this study was to evaluate the anti-inflammatory and anti-angiogenic activities in vitro of eight diterpenoids isolated from Daphne genkwa. LC-MS was used to identify diterpenes isolated from D. genkwa. The anti-inflammatory and anti-angiogenic activities of eight diterpenoids were evaluated on LPS-induced macrophage RAW264.7 cells and TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) using hierarchical cluster analysis (HCA) and principal component analysis (PCA). The eight diterpenes isolated from D. genkwa were identified as yuanhuaphnin, isoyuanhuacine, 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, yuanhuagine, isoyuanhuadine, yuanhuadine, yuanhuaoate C and yuanhuacine. All the eight diterpenes significantly down-regulated the excessive secretion of TNF-α, IL-6, IL-1ß and NO in LPS-induced RAW264.7 macrophages. However, only 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl markedly reduced production of VEGF, MMP-3, ICAM and VCAM in TNF-α-stimulated HUVECs. HCA obtained 4 clusters, containing 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, isoyuanhuacine, isoyuanhuadine and five other compounds. PCA showed that the ranking of diterpenes sorted by efficacy from highest to lowest was 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, yuanhuaphnin, isoyuanhuacine, yuanhuacine, yuanhuaoate C, yuanhuagine, isoyuanhuadine, yuanhuadine. In conclusion, eight diterpenes isolated from D. genkwa showed different levels of activity in LPS-induced RAW264.7 cells and TNF-α-stimulated HUVECs. The comprehensive evaluation of activity by HCA and PCA indicated that of the eight diterpenes, 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl was the best, and can be developed as a new drug for RA therapy.